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Brain Circuitry in Personality Disorders

February 01, 2011

Larry J. Siever, M.D.

From The Quarterly, Winter 2011

Personality disorders, while less known about than some other psychiatric conditions, nonetheless pose serious mental health problems. Researchers are gaining new insights into the brain-circuitry malfunctions that are believed to underlie personality disorders.

Simply stated, people with personality disorders are held back by approaches to life that don’t work, for example, extreme emotions and unstable behavior that constrain their ability to engage others or be effective in the workaday world. Among the various categories of these disorders, borderline personality disorder is characterized by excessive anger, impulsiveness and distorted relationships. People with schizotypal personality disorder are isolated, locked away in their own world. A category called anxious cluster personalities is characterized by people so fearful of and stressed by rejection that they avoid social interactions.

In the human brain, the cortex, which is the region of higher mental function, modulates the more “primitive,” emotional limbic system to create a balance necessary for normal functioning. In psychiatric disorders, including many personality disorders, whether caused by trauma or by abnormal brain-structure development, these systems are not in balance.

Current research is exploring all the elements of brain circuitry that may be disturbed in personality disorders:
• Key anatomical structures, including the cortex and the all-important amygdala, the limbic brain’s alarm center;
• Neurotransmitters, principally serotonin, as well as other molecules of brain-cell communication; and
• Genes that initiate and orchestrate these processes.

Among research findings, PET imaging has revealed a reduction in volume in cortical structure in people with personality disorders. Studies of genes associated with suicide risk, which appear also to be associated with borderline personality disorder, suggest that trauma may amplify the risk for aggression among people with this gene signature.

While personality disorders can change, they tend to change slowly and require psychosocial treatment and in some cases medication. Researchers are exploring therapies such as dialectical behavioral intervention that appears to target the amygdala to help build impulse control and improve emotional processing. Researchers have also been experimenting with the antidepressant fluoxetene (Prozac), which acts on the serotonin system to enhance cortical activity.

Larry J. Siever, M.D.
Professor of Psychiatry,
Director of the Special Evaluation
Program for Mood and Personality Disorders, and Vice-Chair for VA Affairs,
Mount Sinai School of Medicine

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